BIOAVAILABILITY OF SINGLE AND MULTIPLE DOSES OF A NEW ORAL FORMULATION OF 5-ASA IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE AND HEALTHY-VOLUNTEERS

Aims: An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA; mesalazine) has been developed to provide a controlled re lease of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic ava ilability of the drug and its metabolite, acetyl-5-ASA, following sing le (800 mg) and multiple (2400 mg for 56 days) oral dose administratio n. Methods: Three groups were investigated: six healthy volunteers, si x patients with ulcerative colitis, and nine patients with Crohn's dis ease in remission. In the single oral dose study (800 mg) ail three gr oups participated, whereas in the multiple oral dose study (2400 mg/da y for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. Resu lts: In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only a bout 20% of the 5-ASA given was absorbed, with more than 80% of the dr ug being available in the terminal ileum and colon for therapeutic act ivity. The multiple oral dose regimen in patients with inflammatory bo wel disease produced a significantly higher plasma concentration and u rine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher sys temic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse eve nt was reported and laboratory screening tests remained within normal ranges. Conclusions: The new oral 5-ASA formulation is gradually relea sed throughout the small and large intestine, reflected by a low plasm a concentration of the drug and its metabolite, with about 80% of the drug being available for ileum-colon therapeutic activity.